Today we are posting a Flu Puzzle that is very different than previous design puzzles.

The motivation for this puzzle is something we normally have computers do called 'hot spot hashing'. This is a method to dock disembodied amino acids on the surface of a target protein with goal of finding some orientations/residues that score really well. We then take the different clusters and try to find a scaffold protein that can connect residues from each cluster.

It's basically like trying to find a hold on a wall by finding out first good holes to put your fingers into. Our computers normally just randomly dock the amino acids and we expect that with lots of tries eventually we'll find a good contact.

However, this method is often computationally intensive and we want to see if you are able to use your Foldit expertise to just look at the protein and find the best spots.

Please feel free to post any questions in the puzzle comments for 532: Beginner Flu Puzzle: http://fold.it/portal/node/992184

Foldon is a small, 27 residue domain from the C-terminus of a phage virus protein called fibritin. It functions to ensure trimerization and proper folding of the rest of the fibritin domain, but it folds just as capably in isolation. Biophysicists have taken note of its remarkable stability and propensity for trimerization, and have successfully fused foldon to other domains, forming a number of engineered trimeric proteins.

Your job, in this puzzle, is to take an opposite approach. Instead of attaching three copies of a known domain to foldon in order to form a trimer, you’ll be given twenty extra residues extending from foldon’s
N-terminus and asked to fold these chains into a larger trimeric domain that includes foldon. You’ll be allowed to move foldon around as well, but you can only mutate the residues in the polyalanine extension. And remember, three-fold symmetry will be enforced!

Our hope is to synthesize one of your best-scoring structures, in an attempt to generate (via NMR or X-ray crystallography) an experimental structure!

We’ll be using foldon, and some of the larger trimer domains that you generate, in our efforts to make higher-order assemblies: rigid crystals, capsules, and nanowires.